Food allergies, the first of which to occur in life is generally cows' milk allergy, are caused, in most cases, by a reaction to proteins in food. In the early years of life the immune system is still developing and may fail to develop tolerance to dietary antigens (this may also be described as insufficient induction of oral tolerance). The result is that the baby or child or young animal has an exaggerated immune response to the dietary protein and develops an allergic response to it. Food allergies may affect not only humans, but also other mammals such as dogs and cats.
Usually, food hypersensitivity develops just after a susceptible baby, child or young animal first encounters a new food containing potential allergens. Apart from its mother's milk (which can contain food proteins from the mother's diet), the first dietary proteins generally encountered by human babies at least, are cow's milk proteins. Cows' milk allergy (CMA) is the most common food allergy in human babies, affecting approximately 2.5% of all infants [Sicherer S H et al. (2010), Food allergy, Sampson H A, J. Allergy Clin. Immunol. (125)]. Approximately 85% of children out-grow their allergy to cow's milk before the age of 2 to 3 years old. As such, CMA affects other age groups with a lower prevalence.
It is generally accepted that babies with established cows' milk allergy have an increased risk of developing allergies to other dietary proteins such as egg and cereal proteins. These allergies may manifest themselves clinically as atopic diseases such as atopic dermatitis, eczema and asthma. Even those babies who have successfully developed oral tolerance to cows' milk proteins may subsequently develop allergies to other dietary proteins such as egg and cereal proteins when these are introduced into the diet at weaning.
Besides breastfeeding, the primary recommendation for prevention of CMA is the use of partially hydrolyzed hypoallergenic formulae, which are recommended to be prescribed to “at risk” asymptomatic infants, with atopic parents. This approach has been demonstrated to be efficient in preventing sensitization by hydrolyzed proteins (peptides) and residual native (full length) proteins that are present (albeit in a much lower quantity than that in a non-hydrolyzed formula) in the formulae.
Thus, European patent application EP 2 332 428 discloses a formulation comprising a cow's milk peptide-containing hydrolysate capable of inducing oral tolerance. The peptides in question were identified as coming from bovine casein.
There are currently many examples of casein or whey-based partially hydrolyzed hypoallergenic formulae (e.g. NAN®-HA, BEBA®-HA, from Nestlé, and S26®-HA from Wyeth Infant Nutrition) on the market.
For infants already displaying symptoms of CMA, extensively hydrolyzed formulae (e.g. Alfare™, Altéra™ from Nestlé), non-allergenic milk substitute formulae, such as free amino acids (e.g. Alfamino™ from Nestlé) or soy based formulas (such as S26®-Soy, NURSOY™ from Wyeth Infant Nutrition, New York, and NESTLÉ® Good Start® ALSOY® from Nestlé) may be suitable alternatives to cow's milk standard or partially hydrolyzed formulae.
Thus, the primary focus to date in providing nutrition for children with allergies to cow's milk has been to find preparations which will not induce an allergic response, i.e. to provide non-allergenic formulations. One of the drawbacks of administering non-allergenic formulae (containing either free amino acids or extensively hydrolyzed cow's milk proteins) or soya based milk, to infants is that, while such formulations allow infants who are allergic to cow's milk to avoid an allergic response, they do not allow those children to develop oral tolerance to the cow's milk protein allergens so that they can go on to drink unaltered milk products later in life.
Oral tolerance is the specific suppression of cellular and/or humoral immune reactivity to an antigen by prior administration of the antigen by the oral route. It is an important part of the development of the immune system in the first months of life and allows the infant to consume food without adverse reaction. Failure of the establishment of oral tolerance leads to allergy. The development of oral tolerance is linked to the normal immune system education, resulting in a reduced reaction to food antigens.
Several factors have been identified as affecting the induction and maintenance of oral tolerance, among these, the structure of the food protein, the dose and frequency of the antigen administration, as well as the immune status of the host.
To a certain extent, oral tolerance can be induced in infants via breastfeeding [Mosconi E, et al. (2010) Breast milk immune complexes are potent inducers of oral tolerance in neonates and prevent asthma development. Mucosal Immunol; 3:461-74 and Verhasselt et al (2008) Breast milk mediated transfer of an antigen induces tolerance and protection from allergic asthma, Nat Medecine; 14(2): 170-5]. Thus, infants who are breastfed by mothers who have been exposed to and immunized against certain allergenic foods like egg, nuts etc. develop oral tolerance towards these allergens.
Thus, there is a need to further identify the factors that may influence induction of oral tolerance. It is highly desirable to provide hypoallergenic or non-allergenic compositions having an ability to induce and maintain oral tolerance in the infant, to be administered particularly at the weaning period when young mammals are being introduced to new foods.
There is a need to provide nutritional solutions that can prevent or alleviate the development of allergies, especially in infants and toddlers, especially those who are at risk of developing allergy. There is a need to induce tolerance to a variety of allergens including milk, egg, (tree) nuts, peanuts, shellfish, wheat and soy. There is a need to prevent or alleviate the development of allergy during the weaning period when the latter allergens are introduced. There is a need to maintain oral tolerance that has been induced to certain allergens via maternal milk.
There is a need to design and produce nutritional interventions, especially via synthetic ingredients or combinations of ingredients, that can be administered to infants and toddlers, early in life and that reduce the probability or the magnitude of being or becoming allergic or developing allergies later in life.
This need exists for the general population of infants and toddlers and also for sub-populations of infants and toddlers having predisposition to allergies or having declared allergies.
There is a general need to provide relief from allergies or allergy symptoms and to develop means of inducing and maintaining the tolerance to common allergens, such as milk including milk, egg, (tree) nuts, peanuts, shellfish, wheat and soy especially in infants and toddlers.